Cyclization Of N3-Alkynyl-(2-Indol-3-yl) Quinazolin-4(3H)-One To Synthesize 2,3-Fused Quinazolinone Compounds

Nitrogen-containing heterocyclic compounds are one of the most common structural motifs of biologically active molecules including many natural products,and have stimulated increasing interests from the scientific communities due to its pharmaceutical importance.Among the nitrogen-containing heterocyclic scaffolds,quinazolinones derivatives,especially those with 2,3-fused quinazolinones core,represents an important subclass with wide applications in hypnosis,sedation,anticonvulsant,antibacterial,anti-diabetes,anti-inflammatory,anti-tumor,and other drugs.Given their significant importance,many strategies toward the preparing or modifying of compounds have been developed.At present,the synthesis of 2,3-fused quinazolinones mainly involves transition metal catalyzed C-H bond activation,carbonyl insertion cyclization reaction,and intramolecular tandem cyclization.Despite of these achievements,these methods require the use of environmentally unfriendly metal catalysts,and the starting materials of these reactions were difficult to obtain.Therefore,it is still necessary to develop new synthesis methods for quinazolinones and fused quinazolinones derivatives with high efficiency with simple operation and environmental-friendly conditions.This thesis reported the synthesis of two 2,3-fused quinazolinone derivatives using N3-Alkynyl-(2-indol-3-yl)quinazolin-4(3H)-one as raw material under the condition of metal free participation.This dissertation is divided into two parts:In the first part,23 spiroindolenine fused quinazolinone compounds were synthesized through intramolecular spiro cyclization of N3-Alkynyl-(2-indol-3-yl)quinazolin-4(3H)-one under the action of potassium tert-butoxide.At room temperature,with THF as the solvent and the action of potassium tert-butoxide,most substrates can be smoothly converted,obtaining the target compound with a yield of38%-94%.In addition,this reaction can also be studied for large-scale reactions.In the second part,the quinazolinone seven ring fused indole compounds were synthesized from N3-Alkynyl-2-(N-substituted indolyl)quinazolin-4(3H)-one under the action of potassium tert-butoxide.The control experiment showed that the N3-propargyl group generates a diene intermediate under the action of a base,and then an intramolecular cyclization reaction occurred with the methyl group at the C2 position of indole,resulting in the construction of 23 indole fused seven membered ring compounds in a yield of 22%-87%.This reaction is easy to operate,fast to react,and under mild conditions.In addition,it can undergo a large number of reactions and obtain clean products through simple extraction and recrystallization.